Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats

Abstract

Rapamycin is known to extend lifespan. We conducted a randomized placebo-controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin-containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p<.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p<.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans.

Cognitive Reserve in Model Systems for Mechanistic Discovery: The Importance of Longitudinal Studies

“…Grip strength ↓ With age (Fischer et al, 2015;Zhang et al, 2015;Xue et al, 2016;Martinez de Toda et al, 2018;Sheth et al, 2018;Zammit et al, 2019;Febo et al, 2020).…”

“…Longitudinal studies indicate that grip strength decreases throughout aging in mice (Fischer et al, 2015;Zhang et al, 2015;Martinez de Toda et al, 2018;Sheth et al, 2018), rats (Xue et al, 2016;Febo et al, 2020) and humans (Zammit et al, 2019). In humans, grip strength measured late in life is predictive of cognitive decline (Praetorius Bjork et al, 2016;Stijntjes et al, 2017;McGrath et al, 2019).…”

Targeting mitochondrial function and proteostasis to mitigate dynapenia

“…The positive effects of activating energetic signaling on muscle function seem somewhat underappreciated. For example rapamycin treatment, which inhibits mTOR, attenuates the age-related losses of strength, lean body mass, and endurance capacity in mice (Fischer et al 2015; Xue and Leng 2016). In addition, three months of rapamycin treatment directly mitigates dynapenia as measured by improved grip strength and rotarod performance in already aged mice (Bitto et al 2016).…”

Zapalenie starcze - mechanizmy i szlaki sygnałowe

“…W badaniach eksperymentalnych wykazano korzystny wpływ rapamycyny na obniżoną sprawność fizyczną u starych (16-22 miesięczne) szczurów [86]. W badaniach zespołu Correia-Melo i wsp.…”

“…B) W sercach starych myszy SAMP8 wykazano spadek poziomu ATP oraz translokację podjednostek czynnika NF-κB p50, p52, p65 z cytozolu do frakcji jądrowej [73]. C) Podawanie rapamycyny wpływa pozytywnie na sprawność fizyczną u starych szczurów [86] oraz ogólny stan zdrowia u myszy NF-κB1 -/- [87]. D) Komórki MSC starych myszy mimo zmniejszonej ekspresji genów docelowych Notch: Hey 1, Hey L i Hey 2 w pełni reagują na stymulację ligandem Jagged-1 [112].…”